Sarah E. Millar, Ph.D.
Professor of Dermatology
Department: Dermatology
Graduate Group Affiliations
Contact information
M8D Stellar-Chance Labs
422 Curie Blvd
Philadelphia, PA 19104
422 Curie Blvd
Philadelphia, PA 19104
Office: (215) 898-2633
Fax: (215) 573-9102
Fax: (215) 573-9102
Email:
millars@mail.med.upenn.edu
millars@mail.med.upenn.edu
Publications
Education:
B.A. (Biochemistry)
Cambridge University, U.K., 1982.
Ph.D. (Molecular Biology)
University of London, U.K., 1987.
Permanent linkB.A. (Biochemistry)
Cambridge University, U.K., 1982.
Ph.D. (Molecular Biology)
University of London, U.K., 1987.
Description of Research Expertise
Research InterestsDevelopment of hair follicles, mammary glands and teeth; hair follicle and mammary gland stem cells; skin, hair follicle and dental regeneration; skin and mammary gland tumorigenesis; functions of Dicer, Drosha and miRNAs in the skin and mammary glands.
Key words: hair, stem cells, regeneration, skin, tooth, mammary gland, mouse, Wnt, Bmp, beta-catenin, Dicer, miRNA.
Description of Research
Our research is focused on understanding cell-cell signaling mechanisms controlling development, patterning, stem cell function and regeneration in organs such as hair follicles, mammary glands, taste papillae and teeth that arise from embryonic ectoderm (ectodermal appendages). We have shown that WNT/beta-catenin signaling is required for initiating the formation of hair follicles, mammary glands and taste papillae from multipotent cells in the embryonic surface ectoderm. We are using genetic gain and loss of function and microarray approaches to dissect the mechanisms by which Wnt signaling regulates patterning of hair follicles in embryonic skin and to identify direct Wnt target genes in developing hair follicles. We are also interested in understanding the roles played by Wnt/beta-catenin signaling in regulating stem cell function, differentiation, regeneration and tumorigenesis in the adult. For these studies we have developed inducible systems for expression of Dickkopf1 (a potent secreted Wnt inhibitor), deletion of the Wnt effector beta-catenin, and expression of an activated form of beta-catenin, in the epidermis and hair follicle, tooth, tongue and mammary gland epithelia in postnatal mice. We are using these mouse models to determine the effects of gain and loss of Wnt/beta-catenin signaling on hair follicle stem cells and postnatal hair growth; mammary stem cells and postnatal mammary gland development; tooth development, dental stem cells and dental regeneration; taste papilla function; and skin and mammary gland tumorigenesis. We are also using genetic approaches to identify Wnt ligands and receptors required for appendage development, and to investigate the roles played by non-beta-catenin mediated Wnt signaling in the skin. Finally, we have shown that deletion of the miRNA processing enzyme Dicer causes major defects in hair follicle development. We are studying the functions of Dicer and miRNAs in the formation and maintenance of hair follicles and mammary glands.
Rotation Projects for 2009-2010
1. Global approaches to identify direct Wnt target genes in developing hair follicles
2. Mechanisms regulating hair follicle patterning in embryonic ectoderm
3. Functions of miRNAs in maintaining hair follicles and hair follicle stem cells
4. Functions of miRNAs in mammary gland development
5. Manipulation of beta-catenin signaling for dental regeneration
Lab personnel:
Jun-Soo Yun, PhD: Postdoctoral fellow
Yuhang Zhang, PhD: Senior Research Investigator
Xinjiang Wu, PhD: Postdoctoral fellow
Yeon-Sook Choi, PhD: Postdoctoral fellow
Zhenquan Yu, PhD: Research Associate
Matthew Leboeuf: MD PhD thesis student
Monica Teta: PhD thesis student
Matthew Crump: undergraduate student researcher
Hagop (James) Kaprielian: undergraduate student researcher
Sohum Trivedi: undergraduate student researcher
Selected Publications
Zhang Y, Tomann P, Andl T, Gallant NM, Huelsken J, Jerchow B, Birchmeier W, Paus R, Piccolo S, Mikkola ML, Morrisey EE, Overbeek P, Scheidereit C, Millar SE*, Schmidt-Ullrich R*. [*Joint last and corresponding authors.]: Reciprocal requirements for Eda/Edar/NF-kappa B and Wnt/b-catenin signaling pathways in hair follicle induction. Developmental Cell 17, 49-61 2009.Yang, S. H., Andl, T., Gratchchouk, V., Wang, A., Liu, J., Syu, L.-J., Ferris, J, Glick, A. B., Millar, S. E., Dlogosz, A. A.: Pathological responses to oncogenic Hedgehog signaling in skin are dependent on canonical Wnt/beta-catenin signaling. Nat Genetics 40: 1130-1135, August 2008 Notes: Subject of a News and Views article: Nature Genetics 40, 1040-1041 (2008).
Zhang, Y., Andl, T., Yang, S.H., Teta, M., Liu, F., Seykora, J.T., Tobias, J.W., Piccolo, S., Schmidt-Ullrich, R., Nagy, A., Taketo, M.M., Dlugosz, A.A., Millar, S.E.: Activation of beta-catenin signaling programs embryonic epidermis to hair follicle fate. Development 135: 2161-72, June 2008 Notes: Highlighted paper. Epub 2008 May 14.
Liu, F., Chu, E. Y., Watt, B., Zhang, Y., Gallant, N. M., Andl, T., Yang, S., Lu, M-M., Piccolo, S., Schmidt-Ullrich, R., Taketo M. M., Morrisey, E. E., Atit, R., Dlugosz, A. A., Millar, S. E.: Wnt/beta-catenin signaling directs multiple stages of tooth morphogenesis. Dev. Biol. 313: 210-24, 2008.
Liu, F., Thirumangalathu, S., Gallant, N. M., Yang, S. H., Stoick-Cooper, C. L., Reddy, S. T., Andl, T., Taketo, M. M., Dlugosz, A. A., Moon, R. T., Barlow, L. A., Millar, S. E.: Wnt-beta-catenin signaling initiates taste papilla development. Nat Genet. 39: 106-12, 2007.
Stark, J., Andl, T. Millar, S. E. : Hairy Math: Insights into hair-follicle spacing and orientation. Cell 128: 17-20, 2007.
Andl, T., Murchison, E. P., Liu, F., Zhang, Y., Yunta-Gonzalez, M., Tobias, J. W., Andl, C, D., Seykora, J. T., Hannon, G. J., Millar, S. E.: The miRNA processing enzyme Dicer is essential for the morphogenesis and maintenance of hair follicles. Current Biology 6: 1041-9, 2006.
Andl, T., Ahn, K., Kairo, A., Chu, E. Y., Wine-Lee, L., Reddy, S. T., Croft, N. C., Cebra-Thomas, J. A., Metzger, D., Chambon, P., Lyons, K. M., Mishina, Y., Seykora, J. T., Crenshaw, E. B., & Millar, S. E. : Epithelial Bmpr1a regulates differentiation and proliferation in postnatal hair follicles and is essential for tooth development. Development 131: 2257-2268, 2004.
Chu, E. Y., Hens, J., Andl, T., Kairo, A., Yamaguchi, T. P., Brisken, C., Glick, A., Wysolmerski, J. J., & Millar, S. E. : Canonical WNT signaling promotes mammary placode development and is essential for initiation of mammary gland morphogenesis. Development 131: 4819-4829, 2004.
Andl, T., Reddy S. T., Gaddapara, T. & Millar, S. E. : WNT signals are required for the initiation of hair follicle development. Developmental Cell 2: 643-653, 2002.